Abnormal immune mechanisms are being studied in patients with HB Ag negative chronic active hepatitis and primary biliary cirrhosis (PBC) selected according to strict diagnostic criteria. A detailed immunologic evaluation is undertaken. The in vitro cytotoxic capacity of lymphocytes and lymphocyte subpopulations (T, K and B cells) against several liver-specific and non-hepatic target cells in tissue culture is evaluated. In addition, the capacity of the reticuloendothelial system to clear particles from the circulation by non-specific phagocytosis and immunospecific mechanisms is being assessed. Finally, T cell mediated help and suppression of pokeweed-mitogen induced immunoglobulin synthesis is studied in vitro using radioimmunoassays to measure IgG and IgM. Results of these studies include the demonstration in PBC of: (1) reduced spontaneous cytotoxic function of a subpopulation of lymphocytes which lack surface immunoglobulin but bear Fc receptors; (2) impaired C3b-receptor mediated clearance function of Kupffer cells and (3) diminished capacity of T cells to inhibit immunoglobulin synthesis in vitro.